Creation and Validation of the First Infinium DNA Methylation Array for the Human Imprintome.

Area of Science:

• Epigenetics and Genomics
• Developmental Biology
• Disease Mechanisms

Background:

• Differentially methylated imprint control regions (ICRs) regulate imprinted gene expression.
• Epigenetic dysregulation of ICRs by environmental factors contributes to chronic diseases.
• Current methylation arrays inadequately profile ICRs, while whole genome bisulfite sequencing (WGBS) is costly and computationally intensive.

Approach:

• Developed a custom methylation array with 22,819 probes, including 9,757 probes targeting 1,088 candidate ICRs.
• Validated the array by comparing methylation levels with WGBS (mean R² = 0.569) and the Infinium Methylation EPIC v2 array (mean R² = 0.796).
• Demonstrated high reliability through replication experiments (ICC: 0.799-0.945).

Key Points:

• The custom array offers a more accessible and accurate method for profiling ICRs compared to WGBS.
• Achieved good correlation with WGBS and high correlation with the EPIC v2 array for shared CpG sites.
• Exhibits high reliability and reproducibility in methylation assessment.

Conclusions:

• The custom array provides a valuable tool for the accurate and replicable assessment of ICRs.
• Facilitates mechanistic insights and targeted investigations into ICRs.
• Accelerates discovery of ICRs associated with diseases and exposures, advancing understanding of genomic imprinting throughout the life course.